电针刺激足三里对内脏高敏感大鼠的影响及其机制

背景:内脏高敏感是肠易激综合征(IBS)的重要发病机制之一,电针刺激足三里治疗IBS正逐渐应用于临床,然而其对内脏敏感性的影响及其作用机制尚不十分清楚。目的:研究电针刺激足三里对大鼠内脏感觉的影响以及近端结肠、远端结肠和丘脑组织中μ阿片受体蛋白表达的变化,以探讨μ阿片受体在电针治疗IBS中的作用。方法:32只Sprague-Dawley大鼠随机分为正常对照组(NC组)、单纯模型组(M组)、模型+电针组(MEA组)和模型+假电针组(MSE组)。采用直肠灌注乙酸制备内脏高敏感模型。电针(假电针)治疗前后,大鼠行结直肠扩张后记录腹壁肌电。采用蛋白质印迹法检测各组大鼠近端结肠、远端结肠和丘脑组织中μ阿片受体的蛋白表达。结果:与电针刺激前相比,电针刺激后MEA组大鼠在相同结直肠扩张压力(20、40、60、80 mm Hg)下腹外斜肌放电次数均明显减少(P0.001):而MSE组腹外斜肌放电次数无明显差异(P0.05)。与M组相比,MEA组近端结肠、远端结肠和丘脑组织中μ阿片受体蛋白表达明显增加(P0.05),而MSE组无明显差异(P0.05)。结论:电针刺激足三里可降低大鼠内脏高敏感性.其作用机制可能通过上调中枢和外周μ阿片受体蛋白表达而实现的。     

孤啡肽对大鼠体内外结肠动力的影响

目的:探讨孤啡肽受体在结肠运动中的作用. 方法:采用大鼠离体结肠肌条张力测定法、在体结肠肌电测定、炭末推进试验等研究了孤啡肽受体的内源性配基——孤啡肽对大鼠结肠动力的影响．结果:孤啡肽(1-1000 nmol／L)剂量依赖性地引起离体结肠肌条的强直性收缩;孤啡肽(1 μg／ kg)iv诱导在体近端结肠的相位性收缩和基础张力的增加(t=2．41,P=0．02);孤啡肽(3 nmol／ kg)sc加速活性炭悬液通过结肠的转运(48．0± 1．24 vs 43．5±2．63,t=-4．5,P=0．008)．结论:孤啡肽通过一个神经性的非阿片受体介导的机制加速大鼠结肠的收缩和转运,孤啡肽在结肠生理功能中起了一定的作用．     

微生态制剂对内脏高敏感模型大鼠内脏敏感性影响的研究

背景：内脏高敏感在肠易激综合征（IBS）的发病机制中起重要作用,益生菌可调控内脏敏感性,改善IBS的症状。目的：观察微生态制剂对内脏高敏感模型大鼠内脏敏感性的影响,探讨其治疗IBS的可能机制。方法：24只大鼠随机分为正常对照组、模型组、色甘酸钠（DC）组和微生态制剂组。采用急性束缚应激方法诱导内脏高敏感模型。以腹壁回撤反射（AWR）评分检测大鼠内脏敏感性．改良甲苯胺蓝染色法观察结肠黏膜组织肥大细胞脱颗粒情况．ELISA法检测组织和血清组胺、5．羟色胺（5．HT）水平。结果：与正常对照组相比,模型组大鼠内脏敏感性、结肠黏膜肥大细胞数目和脱颗粒比例以及结肠组织和血清组胺、5．HT水平均显著增高（P〈0．01）：经微生态制剂治疗后,上述指标均显著降低（P〈0．01）,且与正常对照组、DC组相比差异均无统计学意义（P〉0．05）。结论：微生态制剂可降低大鼠内脏高敏感,可能与其抑制结肠黏膜肥大细胞脱颗粒,降低结肠组织和血清组胺、5-HT水平有关。     

硫化氢对结、直肠扩张大鼠内脏痛觉及P物质表达影响的研究

目的 研究硫化氢对结、直肠扩张大鼠内脏伤害性感觉及P物质表达的影响。方法Wistar大鼠40只按体质量分层随机均分为5组：对照组、0．9%氯化钠溶液组、硫氢化钠（NaSH）低剂量组（15μmol／kg）、中剂量组（45μmol／kg）及高剂量组（75μmol／kg）。除对照组外，其余各组应用结、直肠内球囊扩张（CRD）法，持续扩张25S，并进行行为测评。取大鼠回盲部、结肠、脊髓胸腰段（T6～L5）及脑标本进行组织化学染色检测P物质。结果在0．9%氯化钠溶液组大鼠，由结、直肠扩张所致的内脏痛出现容量依赖的腹部撤离反射（AWR）分数上升，腹腔注射NaSH后出现剂量依赖的AWR分数减低。结、直肠扩张后，0．9％氯化钠溶液组与NaSH低剂量组大鼠结肠、回盲部、脊髓胸段、腰段及丘脑中P物质表达升高，但差异无统计学意义（P〉0．05），而NaSH中、高剂量组P物质表达比0．9％氯化钠溶液组显著减少（P〈0．01）。结论 硫化氢能降低结、直肠扩张大鼠的伤害性感觉，并呈量效关系。应用CRD建立的内脏伤害性感觉的动物模型，硫化氢可下调肠黏膜下、肌间 神经丛、脊髓背角和丘脑P物质表达。     

辣椒素对内脏痛觉过敏的影响及其机制

辣椒素(capsaicin,CAP)药理作用广泛,其对内脏痛觉过敏(visceral hyperalgesia,VHL)的影响已引起广大学者的关注.研究显示小剂量CAP可能诱发VHL,而大剂量的CAP可能对VHL有抑制作用.CAP对VHL的作用机制可能与CAP受体(vanilloid receptor subtype 1,VR1)及其VR1的磷酸化和去磷酸化、P物质(SP)、降钙素基因相关肽(CGRP)、蛋白水解酶激活型受体2(protease-activated receptor 2,PAR2)等有关.CAP可能成为一种有前景的治疗VHL的新药.     

雌激素对大鼠内脏高敏感形成和P2X3 mRNA表达的影响

背景：雌激素可能与女性肠易激综合征（IBS）的高发病率有关，P2X3受体在介导痛觉中发挥重要作用。目的：探讨雌激素对避水应激大鼠内脏高敏感形成和P2X3 mRNA表达的影响。方法：雌性Wistar大鼠避水或假避水应激10d，每天1h，每次应激或假应激前30min侧脑室注射17β-雌二醇（E2）或0．9％NaCl溶液（NS）1．0μg，以结直肠扩张时的内脏运动反射（VMR）幅度值为指标观察内脏敏感性的变化。取避水应激大鼠的L1和S1背根神经节行P2X3免疫荧光染色，比较P2X3免疫阳性细胞数，荧光实时定量聚合酶链反应（PCR）比较两组大鼠L1至S2背根神经节P2X3 mRNA的表达。结果：应激或假应激后，E2应激组的VMR幅度值较应激前显著升高，NS应激组以及E2假应激组和NS假应激组均无显著变化。E2应激组的背根神经节P2X3阳性细胞数[（38．38±3．31）％]显著高于NS应激组[（33．20±2．85）％1（P〈0．01），P2X3 mRNA表达（0．97±0．81）亦显著高于NS应激组（0．22±0．14）（P〈0．05）。结论：背根神经节P2X，受体可能参与了雌激素和避水应激所致的内脏高敏感过程。     

内脏高敏感大鼠脑部5-羟色胺表达差异的研究

自1973年Ritchie报道了肠易激综合征患者结肠气囊扩张疼痛阈值下降以来,内脏高敏感这一致病机制备受关注,但对内脏高敏感发生的原因和机制尚缺乏深入研究.研究显示,内脏高敏感大鼠结肠和脊髓5-羟色胺（5-HT）表达增加,但高级中枢5-HT表达情况尚未见报道.我们通过建立内脏高敏感大鼠模型,研究大脑中5-HT分布和表达情况.     

Nesfatin-1对内脏高敏感大鼠内脏敏感性影响机制的研究

目的研究Nesfatin-1对内脏高敏感大鼠血液、脑肠轴组织5-HT表达的影响,探讨Nesfatin-1对内脏高敏感大鼠内脏敏感性影响的机制,为进一步明确内脏高敏感形成机制的研究提供思路。方法将新生2 d龄雄性SD大鼠随机分为健康对照组和模型组,模型组大鼠通过母婴分离和醋酸灌肠相结合的方法制备内脏高敏感大鼠模型。模型验证成功后,模型组分为干预对照组、低浓度干预组、中浓度干预组和高浓度干预组,应用IHC、ELISA、Western blotting方法检测内脏高敏感模型大鼠血液、脑肠轴不同部位5-HT的表达,对实验结果进行统计学分析。结果 (1)不同分组大鼠血清5-HT水平的ELISA检测结果:健康对照组、干预对照组大鼠分别与低浓度组、中浓度组、高浓度组比较,大鼠血清5-HT水平差异有统计学意义(P0.05)。(2)不同分组大鼠脑肠轴组织5-HT表达IHC检测结果:健康对照组、干预对照组分别与低浓度组、中浓度组、高浓度组比较,结肠组织、脊髓组织、脑组织中5-HT阳性表达差异有统计学意义(P0.05),Nesfatin-1不同浓度组大鼠脑肠轴5-HT阳性表达明显高于健康对照组、干预对照组。(3)不同分组大鼠脑肠轴组织5-HT表达Western blotting检测结果:健康对照组、干预对照组分别与低浓度组、中浓度组、高浓度组比较,结肠组织、脊髓组织、脑组织中5-HT表达差异有统计学意义(P0.05)。结论 Nesfatin-1通过中枢途径干预内脏高敏感大鼠,发现Nesfatin-1可以上调内脏高敏感大鼠血液、脑肠轴不同部位5-HT水平,推测Nesfatin-1可能通过上调5-HT的水平影响中枢和外周5-HT信号通路,最终参与内脏高敏感的形成及调控。     

辣椒素受体对肠易激综合征内脏痛觉过敏的影响

功能性胃肠疾病是近年来导致消化病谱变化的主要因素,其中肠易激综合征(IBS)是常见的功能性胃肠病之一,其发病机制尚未阐明,目前内脏高敏感性被认为是最主要的发病机制.辣椒素及辣椒素受体对痛觉过敏的作用已受到越来越多的关注.此文就辣椒素及辣椒素受体对IBS内脏高敏感的研究进展作一综述.     

甜味素对复合法制备大鼠肝硬化模型的影响

肝硬化动物模型是肝硬化的研究基础,研究肝硬化的发生机制及其防治必须建立良好的动物模型.目前,国内外制备肝硬化模型方法虽较多,但死亡率较高,成模率较低.本研究对目前最常用的复合法制备肝硬化模型的方法进行了改良,提高了肝硬化成模率、降低了大鼠死亡率.     

Effects of nociceptin/orphanin FQ on rats with cathartic colon

AIM To demonstrate the change and effect of nociceptin/orphanin FQ in the colon of rats with cathartic colon.METHODS The cathartic colon model was established by feeding rats rhubarb for 3 mo, the changes of colonic electromyography were investigated by both suspension muscle strips test and serosal recordings of colonic myoelectrical activity. Immunohistochemical staining (S-P methods) and image analysis were used to determine the changes of nociceptin/orphanin FQ in the proximal colon and distal colon of rats with cathartic colon.RESULTS Suspension muscle strips test in vitro showed OFQ (10-9-10-6 mol/L) concentration dependently caused an immediate tonic contraction in the isolated colon. But the increase of tension in cathartic colon was less than control groups (P＜0.01). Intravenous administration of OFQ (1μg/kg) caused phasic contractions in the proximal colon, while the amplitude of phasic contractions caused by OFQ in cathartic colon was much lower than that in the control groups (2.58 ± 0.41 vs 4.16± 0.53, t= -2.6, P = 0.012). OFQ was highly expressed in the myenteric plexus of the rat colon but not in the muscle cells. The immunoreactivity of OFQ in the proximal colon in cathartic colon rats decreased significantly compared with the control group (P = 0.001).CONCLUSION Colonic smooth muscle of cathartic colon showed low sensitivity to the stimulation of OFQ, suggesting that it might be caused by the abnormal distribution of OFQ or the abnormalities of receptors, leading to the disorganization of dynamic and incoordinated contractions.     

Antitussive effect of nociceptin/orphanin FQ in experimental cough models

Cough is an important defensive pulmonary reflex that removes irritants, fluids or foreign materials from the airways. However, often cough is non-productive and requires suppression. Opioid mu receptor agonists, such as codeine are commonly used as antitussive agents and are among the most widely administered drugs in the world. Codeine suppresses the responsiveness of one or more components of the central reflex pathway for cough and is an efficacious antitussive drug for cough due to diverse aetiologies. However, opioids produce side effects that include sedation, addiction potential and constipation. Therefore, novel cough suppressant therapies should maintain or improve upon the antitussive efficacy profile of opioids. Moreover, these novel therapies should have a safety profile significantly better than current antitussive therapies. Presently, we discuss preclinical findings showing that activation of the 'opioid-like' receptor (NOP(1)) inhibits cough in the guinea pig and cat.     

Low utility of plasma Nociceptin/orphanin FQ in the diagnosis of hepatocellular carcinoma

AIM: The utility of serum alpha-fetoprotein (alpha-FP) in the detection of hepatocellular carcinoma (HCC) is questionable. Very high circulating levels of nociceptin/orphanin FQ (N/OFQ), a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis. METHODS: Plasma N/OFQ levels were measured by ELISA in 58 patients (28 HCC and 30 liver cirrhosis) and in 25 healthy controls. The values were correlated with clinical and laboratory features including alpha-FP. Spearman index, biserial correlation coefficient, non parametric combination (NPC) test and discriminant stepwise analysis were used for statistical evaluation of data. RESULTS: The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. alpha-FP serum levels > 200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including alpha-FP. By NPC test, HCC and cirrhotic patients were different with regard to alpha-FP (P = 0.000) but not in terms of nociceptin (P = 0.595). By point biserial correlation, HCC presence was positively correlated with alpha-FP (rpb = 0.52, P = 0.000) but not with N/OFQ (rpb = 0.16, P = 0.157). In a discriminant analysis, alpha-FP was significant in the Wilks test (Y = -0.709 + 0.03 alpha-FP) and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than alpha-FP. CONCLUSION: Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.     

Minireview: Characterization of influence of central nociceptin/orphanin FQ on consummatory behavior

Nociceptin/orphanin FQ (N/OFQ), a peptide closely related to dynorphin A, is the endogenous agonist of the NOP receptor that moderately increases food intake under various conditions. Its orexigenic properties are mediated by the brain circuitry. In the present review, we focus on discussing the nature of hyperphagic effects of N/OFQ with special emphasis on its function within feeding-related neural networks. Although some of N/OFQ's orexigenic effects resemble those induced by opioids, reward-dependent feeding appears to be affected in a different manner by agonists of the NOP and classical opioid receptors. Also, data suggest that N/OFQ may not only promote feeding initiation, but rather its role may be to inhibit signaling responsible for inhibition of consummatory behavior. Central systems involved in termination of feeding that seem to be influenced by N/OFQ encompass oxytocin, alpha-MSH, and CRH.     

A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat

The biochemical and behavioral effects of a nonpeptidic, selective, and brain-penetrant agonist at the ORL1 receptor are reported herein. This low molecular weight compound [(1S,3aS)-8- (2,3,3a,4,5, 6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza- spiro[4. 5]decan-4-one] has high affinity for recombinant human ORL1 receptors and has 100-fold selectivity for ORL1 over other members of the opioid receptor family. It is a full agonist at these receptors and elicits dose-dependent anxiolytic-like effects in a set of validated models of distinct types of anxiety states in the rat (i.e., elevated plus-maze, fear-potentiated startle, and operant conflict). When given systemically, the compound has an efficacy and potency comparable to those of a benzodiazepine anxiolytic such as alprazolam or diazepam. However, this compound is differentiated from a classical benzodiazepine anxiolytic by a lack of efficient anti-panic-like activity, absence of anticonvulsant properties, and lack of effects on motor performance and cognitive function at anxiolytic doses (0.3 to 3 mg/kg i.p.). No significant change in intracranial self-stimulation performance and pain reactivity was observed in this dose range. Higher doses of this compound (>/=10 mg/kg) induced disruption in rat behavior. These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ/nociceptin neuropeptide given locally into the brain and support a role for orphanin FQ/nociceptin in adaptive behavioral fear responses to stress.     

不同饲料配方及喂饲方法制备不同胰岛素敏感性大鼠模型的研究

目的使用不同饲料配方及喂饲方法制备具有不同胰岛素敏感性（IS）的大鼠模型方法132只雄性SD大鼠分为3组（对照组、肥胖组、限食组）,使用两种饲料（基础与高脂高能）及两种喂饲方式（自由与限食）喂饲6个月.各组大鼠在喂饲至2个月、4个月、6个月时采用正常血糖、高血浆胰岛素钳夹技术检测IS并进行口服糖耐量试验;同时检测大鼠体重、内脏体脂重量及空腹血浆胰岛素（FIns）水平.结果在此喂饲条件下,各组大鼠IS由高到低依次为：限食组＞对照组＞肥胖组.肥胖组大鼠喂饲2个月时就已出现IS明显减退（55%）和糖耐量受损,并随喂饲时间延长而加重;对照组大鼠喂饲2个月、4个月时IS与糖耐量结果正常,6个月时糖耐量与IS有所减退;限食组大鼠始终保持胰岛素高敏状态,实验结束时,该组大鼠IS分别为对照组和肥胖组的5倍与10倍.三组大鼠的体重、体内脂肪含量及血浆胰岛素水平均有相应的变化.结论本实验采用的不同饲料及喂饲方式可以成功地制备稳定可靠的、具有不同IS的大鼠模型.     

Hybrid方法建立肺血减少型先天性心脏病幼猪动物模型

目的 研究肺血减少型先天性心脏病(先心病)肺血管发育的病理生理过程及其相关调节机制,探讨肺血减少型先心病幼猪动物模型构建的可行性方法.方法 采用出生1～2个月的幼猪共20只,按照购入时的编号顺序(1～20),随机分为3组:(1)对照组(C组,n=6),右胸前外侧切口造成一过性肺血减少;(2)轻中度狭窄组(T1组,n=7),右胸前外侧切口经右心房表面送入球囊扩张器行人工房间隔造口+肺动脉Banding环缩术,术中收缩期肺动脉环缩处压差(systolic trans pulmonary artery banding pressure,Trans-PABP)20～30 mm Hg(1 mm Hg=0.133 kPa);(3)重度狭窄组(T2组,n=7),术中Trans-PABP≥30～50 mm Hg.术后1个月行64排CT扫描评估,2个月二次开胸手术测定动脉血气分析及血常规,测量各组血管直径及Trans-PABP,处死动物切取心肺组织测量房间隔缺损(ASD)和Banding环直径.结果 C组动物因麻醉意外,术后10 h死于呼吸衰竭1例.T1组术后21 d死于肠梗阻、肠坏死1例.T2组死亡2例,分别于术后24 b和39 d因急性和慢性右心功能衰竭死亡.T1和T2组存活动物房间隔造口+肺动脉环缩术均获得成功.术后超声测定T1和T2组房缺大小分别为(8.0±0.5)mm、(8.9±1.4)mm(P＞0.05),Trans-PABP术后至2个月持续显著增加,T1组由(19.1±5.6)mm Hg增加至(24.1±3.0)mm Hg(P＜0.01),T2组由(34.2±3.9)mm Hg增加至(43.6±6.4)mm Hg(P＜0.01).术前三组间氧分压(PaO2)和血细胞比容(Hct)差异均无统计学意义.术后2个月T1、T2组PaO2显著低于C组,且T2组低于T1,T1、T2组Hct显著高于C组,且T2组高于T1组(P＜0.05).64排CT扫描示T1组主动脉直径(AOD)明显低于C组,T1、T2组肺动脉环缩处直径显著低于各自的AOD(P＜0.01).结论 采用球囊扩张房间隔造口+肺动脉环缩的方法成功的建立了理想的肺血减少型先心病模型,该模型简单可靠、经济实用,十分接近临床的病理生理状态,为该类疾病的临床研究奠定了坚实的实验基础.

Abstract：

Objective To establish an animal model of congenital heart defect with decreased pulmonary blood flow for better understanding the pathophysiology of pulmonary vascular development and related regulatory mechanisms of congenital heart defect with decreased pulmonary blood flow. Method One to two months old pigs were randomly divided into three groups: control group(group C, n = 6)with right chest small incisions induced transient pulmonary blood reduction;light-moderate stenosis groups (group T1, n = 7):artificial atrial septum defect(ASD)plus controlled pulmonary artery banding to generate a systolic pressure gradient of 20-30 mm Hg(1 mm Hg = 0. 133 kPa);severe stenosis groups (group T2, n = 7): similar surgical procedures as group T1, and controlled pulmonary artery banding to generate a systolic pressure gradient ≥ 30 ～50 mm Hg. 64-slice computed tomography scanning was performed at one month post operation. Arterial blood gas analysis, hemoglobin value, pulmonary vessel,ASD and banding ring diameters and trans-pulmonary artery banding pressure(Trans-PABP)were determined at two months post operation. Results One pig died due to tracheal intubation accident in the C group, one pig died due to bowel obstruction in the T, group and two pigs died due to acute right heart failure and chronic heart failure respectively in T2 group. 64-slice CT angiography results showed that aortic diameter of T1 group was significantly lower than that of C group and banding diameter was significantly lower than aortic diameter in the T1 and T2 groups at one month post operation. Two months after operation, the size of ASD were(8.0 ± 0. 5)mm and(8.9 ± 1.4)mm(P ＞ 0. 05)respectively in the T1 and T2 groups after operation. The Trans-PABP was significantly higher in the T1 and T2 groups than in C group(P ＜0. 01), and the Trans-PABP was significantly higher in the T2 group than in T1 group(P ＜0. 01). PaO2 and SaO2 in the T1 and T2 groups were significantly lower than those in C group. Conclusion Artificial atrial septum defect combined pulmonary artery banding procedures could be successfully used to establish model of congenital heart defect with decreased pulmonary blood flow and this model could help to understand the pathophysiology and monitor therapy efficacy for patients with congenital heart defect with decreased pulmonary blood flow.     

替加色罗对内脏感觉过敏大鼠模型的抗伤害性感觉作用

目的　了解结直肠机械刺激对大鼠内脏感觉功能的影响以及替加色罗对大鼠内脏感觉功能的调节作用。方法　 8～ 2 1日龄大鼠每天行结直肠扩张 (CRD组 ,压力 6 0mmHg) ,对照组仅用导管在肛门周围轻微接触。 8～ 1 0周龄时用自制气囊扩张大鼠降结肠和直肠 ,观察动物的腹壁回撤反射(AWR)以测定内脏感觉。选取 8～ 1 0周龄的雄性大鼠分为CRD组、对照组和溶媒对照组 ,观察腹腔注射替加色罗前后的AWR评分。结果　扩张压力与AWR评分显著相关 (P <0 .0 1 ) ;CRD组在 4 0、6 0、80mmHg的压力扩张下 ,AWR评分明显高于对照组 (1 .96± 0 .1 6比 1 .36± 0 .1 6、2 .82± 0 .1 3比 2 .1 7± 0 .1 4、3.2 1± 0 .1 4比 2 .5 9± 0 .1 4 ,P <0 .0 1 ) ;在 4 0、6 0、80mmHg扩张压力下 ,CRD组的AWR评分在用替加色罗后较用药前明显降低 (1 .95± 0 .5 0比 1 .32± 0 .5 5、3.0 5± 0 .4 8比 2 .32± 0 .5 4、3.2 5± 0 .6 3比 2 .77± 0 .5 1 ,P <0 .0 5 ) ;对照组和溶媒对照组的AWR评分在用药前后差异无显著性。结论　新生大鼠给予结直肠机械刺激在成年后可导致慢性内脏感觉过敏 ;替加色罗通过提高对结直肠扩张的疼痛阈值 ,具有抗伤害性感觉作用